The 14-bp deletion in the HLA-G gene indicates a low risk for acute cellular rejection in heart transplant recipients

Twito, Tal; Joseph, Jemy; Mociornita, A.G.; Rao, Vivek; Ross, Heather J.; Delgado, Diego

doi:10.1016/j.healun.2011.01.726

Cited by 41 publications

(22 citation statements)

References 28 publications

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“…Our findings are also in agreement with the majority of expression studies of HLA-G in solid organ transplantation evidencing the beneficial effect of HLA-G molecules against acute rejection/chronic dysfunction of the transplanted heart and kidney (Lila et al, 2000, 2002; Crispim et al, 2008a) and also with those establishing correlations between the presence of the HLA-G 14 bp Ins allele and organ rejection (Crispim et al, 2008b; Piancatelli et al, 2009; Twito et al, 2011). …”

Section: Discussionsupporting

confidence: 82%

Association of HLA-G Low Expressor Genotype with Severe Acute Graft-Versus-Host Disease after Sibling Bone Marrow Transplantation

Boukouaci¹,

Busson²,

Fortier³

et al. 2011

Front. Immun.

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Background: Human leukocyte antigen-G (HLA-G) molecules play a prominent role in immune tolerance. Structurally similar to their classical HLA homologs, they are distinct by having high rate of polymorphism in the non-coding regions including a functionally relevant 14-base pair (bp) insertion/deletion (Ins/Del) allele in the 3′ untranslated region (3′UTR), rarely examined in a hematopoietic stem cell transplantation (HSCT) setting. Here, we analyzed the potential impact of HLA-G Ins/Del dimorphism on the incidence of acute graft-versus-host disease (aGvHD), transplant-related mortality (TRM), overall survival (OS), and incidence of relapse after HSCT using bone marrow (BM) as stem cell source from HLA-matched donors. Methods: One hundred fifty-seven sibling pairs, who had undergone HSCT, were studied for the distribution of the HLA-G 14 bp Ins/Del polymorphism using a polymerase chain reaction (PCR)-based technique. Potential genetic association with the incidence of aGvHD, TRM, and OS was analyzed by monovariate and multivariate analyses. Results: Monovariate analysis showed that the homozygous state for the 14-bp Ins allele is a risk factor for severe aGvHD (grade III and IV; P = 0.008), confirmed subsequently by multivariate analysis [hazard ratio (HR) = 3.5; 95% confidence interval (95%CI) = 1.3–9.5; P = 0.012]. We did not find any association between HLA-G polymorphism and the other studied complications. Conclusion: Our data suggest that the HLA-G low expressor 14 bp Ins allele constitutes a risk factor for the incidence of severe aGvHD in patients who received BM as stem cell source.

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Section: Discussionsupporting

confidence: 82%

Association of HLA-G Low Expressor Genotype with Severe Acute Graft-Versus-Host Disease after Sibling Bone Marrow Transplantation

Boukouaci¹,

Busson²,

Fortier³

et al. 2011

Front. Immun.

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“…But to date, there is still conflicting data regarding the influence of HLA‐G 14‐bp ins/del polymorphism on sHLA‐G expression levels. In general, the 14 bp Ins/Ins was associated with significantly lower sHLA‐G level in plasma or serum (Chen et al, ; Hviid et al, ; Inès et al, ; Rizzo et al, ; Twito et al, ). However, Sakly et al () showed that there was no association between HLA‐G 14 bp polymorphism and sHLA‐G plasma level in Tunisian patients with Behcet's disease.…”

Section: Discussionmentioning

confidence: 99%

Human leucocyte antigen‐G 14‐bp InDel polymorphism and oral squamous cell carcinoma risk in Chinese Han population: A case–control study

Wang

Zhao

Liu

et al. 2018

Int J Immunogenetics

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Human leucocyte antigen-G (HLA-G) is a nonclassical HLA class I molecule involved in tumour immune escape. The purpose of this study was to investigate the association between the 14-bp insertion/deletion (InDel) polymorphism in the 3' untranslated region (3'-UTR) of HLA-G gene and oral squamous cell carcinoma (OSCC) risk in Chinese Han population (216 cases and 193 healthy controls), and furthermore, to evaluate serum soluble HLA-G (sHLA-G) levels in the OSCC patients. Our results demonstrated that the Ins allele was significantly less frequent in the OSCC patients than that in the healthy controls (odds ratio [OR] = 0.75; 95% confidence interval [CI]: 0.57-0.99; p = 0.040). Distribution of the 14-bp genotypes in the OSCC patients and the healthy controls revealed that the Ins/Ins genotype was associated with decreased OSCC risk in both the codominant model (Ins/Ins versus Del/Del; OR = 0.57; 95% CI = 0.33-0.99; p = 0.044) and the log-additive model (OR = 0.76; 95% CI: 0.58-0.99; p = 0.044). The serum sHLA-G level was significantly higher in the OSCC patients than those in the healthy controls (p < 0.001). Receiver operating characteristic (ROC) curve revealed the valuable diagnostic value of sHLA-G for OSCC detection, with an area under the ROC curve (AUC) of 0.891 (95% CI: 0.856-0.925, p < 0.001). The OSCC patients with Ins/Ins genotype had lower serum sHLA-G levels than those with Ins/Del and Del/Del genotypes (p = 0.015). Furthermore, serum sHLA-G levels were significantly increased with the increasing TNM stages of the OSCC patients (p = 0.017). Our findings revealed that the HLA-G 14-bp InDel polymorphism might be a genetic risk factor for OSCC susceptibility, and the serum sHLA-G may act as a promising biomarker for noninvasive diagnosis of OSCC.

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“…On the other hand in healthy individuals [144] and in heart transplantation, the highest production of sHLA-G has been related to the 14 bp deletion/deletion genotype in pre- and posttransplantation resulting in low rejection rates. In addition, the 14 bp polymorphism of the HLA-G gene is related to the cyclosporine absorption of the patient [145, 146]. …”

Section: The Impact Of the Genetic Background On Hla-g Expression mentioning

confidence: 99%

HLA-G as a Tolerogenic Molecule in Transplantation and Pregnancy

Rebmann

Nardi

Wagner

et al. 2014

Journal of Immunology Research

101

113

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HLA-G is a nonclassical HLA class I molecule. In allogeneic situations such as pregnancy or allograft transplantation, the expression of HLA-G has been related to a better acceptance of the fetus or the allograft. Thus, it seems that HLA-G is crucially involved in mechanisms shaping an allogeneic immune response into tolerance. In this contribution we focus on (i) how HLA-G is involved in transplantation and human reproduction, (ii) how HLA-G is regulated by genetic and microenvironmental factors, and (iii) how HLA-G can offer novel perspectives with respect to therapy.

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The 14-bp deletion in the HLA-G gene indicates a low risk for acute cellular rejection in heart transplant recipients

Cited by 41 publications

References 28 publications

Association of HLA-G Low Expressor Genotype with Severe Acute Graft-Versus-Host Disease after Sibling Bone Marrow Transplantation

Association of HLA-G Low Expressor Genotype with Severe Acute Graft-Versus-Host Disease after Sibling Bone Marrow Transplantation

Human leucocyte antigen‐G 14‐bp InDel polymorphism and oral squamous cell carcinoma risk in Chinese Han population: A case–control study

HLA-G as a Tolerogenic Molecule in Transplantation and Pregnancy

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